The development and application of vaccines for use in humans has had numerous shortcomings. To date, the adjuvants that have been best characterized include Freund's complete and incomplete adjuvant, and alum. Freund's and its variations have shown much promise in inducing immunostimulation and enhancing specific immune responses against protein antigens. However, it is presently not acceptable for use in humans due to unacceptable tissue damage and necrosis following its application (Aucouturier et al., Vaccine 19: 2666-2671 (2001)). Similar results have been found with incomplete Freund's, which lacks some pathogenic material. The alternative, alum, has a good safety record, but it is a weak adjuvant for the induction of antibodies against protein antigens (O'Hagan et al., Biomolecular Engineering 18: 69-85 (2001)). Moreover, alum adjuvants can induce IgE antibody response and have been associated with allergic responses in some subjects.
Located preferentially at the host's interface with the surrounding environment, mast cells have the capacity to rapidly release many presynthesized mediators e.g. TNF-α, histamine, and tryptase, which are stored within abundant, specialized intracellular granules (J. Marshall and J. Bienenstock, Curr Opin Immunol 6, 853-9 (December, 1994)). Because of their intrinsic capacity to undergo repeated cycles of degranulation and regranulation, mast cells are major mediators of inflammation in the host. Indeed, mast cells have been implicated in several pathophysiological conditions including, asthma, allergy, inflammatory bowel disease and arthritis (l). More recently, mast cells were reported to mediate the recruitment of neutrophils to sites of bacterial infection through this rapid release of TNF-α, which represents a critical physiological role for these cells and this cytokine in the innate immune response to infection (R. Malaviya et al., Abraham, Nature 381, 77-80 (May 2, 1996); B. Echtenacher et al., Nature 381, 75-7 (May 2, 1996)).
Draining nodes are dynamic lymphoid structures capable of entrapping large numbers of circulating lymphocytes in response to inflammatory stimuli. Within swollen nodes, newly recruited T cells interact with antigen loaded antigen presenting cells, a process which initiates the highly evolved adaptive immune system (M. K. Jenkins et al., Annu Rev Immunol 19, 23-45 (2001)). Currently, the exact mechanisms controlling lymph node hypertrophy in response to peripheral infection remain largely unknown.